Epstein-Barr Virus – Is the Culprit of MS Revealed?
Could the Epstein-Barr virus hold the answer to the etiology of multiple sclerosis? A dataset of over 10 million American recruits offered intriguing insights. You may have encountered the conclusions of one of the most extensive studies in modern history in the media. Let's take a closer look at the work of Kjetil Bjornevik and his colleagues.
EBV as the Main Suspect
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, likely having a multifactorial etiology. However, the most probable dominant trigger seems to be a virus − specifically, the Epstein-Barr virus (EBV) has long been suspected in this context. The ubiquitous nature of EBV, which infects 95% of adults, and the fact that MS is a relatively rare disease, have so far prevented valid confirmation of this theory. Bjornevik et al. gained access to blood samples from 10 million US military members, which are taken in regular two-year intervals and subsequently archived.
Methodology and Results
The authors of the study analyzed samples from 1993−2013. At the time of the first sample (before service commencement), the majority of individuals were under 20 years old, and as expected, approximately 5.3% of them were EBV-negative. During the observation period, MS occurred in a total of 955 military personnel, on average, 10 years after joining the service. Their samples were compared with those of two randomly selected individuals without MS, matched for age, ethnicity, military specialization, and sampling times.
Of the group of people who developed MS, there were 35 EBV-negative initial samples, compared to 107 in the healthy controls. One year before the onset of MS, only one soldier who later developed MS remained EBV-negative. The median time from the first EBV-positive sample to MS onset was 5 years. The high seroconversion rate among individuals who developed MS during the follow-up (97%) contrasts with the 57% seroconversion rate observed among individuals who did not develop MS.
Clinical Manifestations as the Tip of the Iceberg
The authors aimed to elucidate the events preceding the clinical onset of MS. To uncover the temporal relationship between EBV infection and MS, they measured serum concentrations of neurofilament light chains (sNfL) from the collected samples, a marker of neuroaxonal degeneration. Previous studies showed that sNfL levels rise on average 6 years before the clinical manifestation of MS. In this study, no signs of neuroaxonal degeneration were found before EBV seroconversion in individuals who later developed MS; their sNfL levels were comparable to those of healthy controls. However, after seroconversion, their sNfL levels increased. This indicates that EBV infection preceded not only the onset of symptoms but also the emergence of the earliest detectable pathological mechanisms underlying MS.
Conclusion
This study is the most compelling evidence yet that EBV contributes to the development of multiple sclerosis. Specifically, the data indicate a 32× higher risk of developing MS in EBV-positive individuals. However, it cannot be said that EBV is the sole factor causing the development of MS. The virus is, nonetheless, demonstrably one of the initial triggers of pathological mechanisms. This could potentially open the door to preventing MS by averting the development of this infection.
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Source: Bjornevik K., Cortese M., Healy B. C. et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 2022; 375 (6578): 296−301, doi: 10.1126/science.abj8222.
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